Height, Obesity, and the Risk of TMPRSS2:ERG-Defined Prostate Cancer.

Abstract

Background: The largest molecular subtype of primary prostate cancer is defined by the TMPRSS2:ERG gene fusion. Few studies, however, have investigated etiologic differences by TMPRSS2:ERG status. Because the fusion is hormone-regulated and a man's hormonal milieu varies by height and obesity status, we hypothesized that both may be differentially associated with risk of TMPRSS2:ERG-defined disease.Methods: Our study included 49,372 men from the prospective Health Professionals Follow-up Study. Participants reported height and weight at baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG protein expression (a TMPRSS2:ERG marker) was immunohistochemically assessed. We used multivariable competing risks models to calculate HRs and 95% confidence intervals (CIs) for the risk of ERG-positive and ERG-negative prostate cancer.Results: During 23 years of follow-up, we identified 5,847 incident prostate cancers, among which 913 were ERG-assayed. Taller height was associated with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95% confidence interval (CI), 1.03-1.50; Pheterogeneity = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m2 HR 0.75; 95% CI, 0.61-0.91; Pheterogeneity = 0.02) and updated BMI over time (per 5 kg/m2 HR 0.86; 95% CI, 0.74-1.00; Pheterogeneity = 0.07) were associated with a reduced risk of ERG-positive disease only.Conclusions: Our results indicate that anthropometrics may be uniquely associated with TMPRSS2:ERG-positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk.Impact: Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes. Cancer Epidemiol Biomarkers Prev; 27(2); 193-200. ©2017 AACR.

• Authors: Rebecca E Graff, Thomas U Ahearn, Andreas Pettersson, Ericka M Ebot, Travis Gerke, Kathryn L Penney, Kathryn M Wilson, Sarah C Markt, Claire H Pernar, Amparo G Gonzalez-Feliciano, Mingyang Song, Rosina T Lis, Daniel R Schmidt, Matthew G Vander Heiden, Michelangelo Fiorentino, Edward L Giovannucci, Massimo Loda, Lorelei A Mucci
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 27 Issue 2 Pg. 193-200 (02 2018) ISSN: 1538-7755 [Electronic] United States
• PMID: 29167279 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• ERG protein, human
• Oncogene Proteins, Fusion
• TMPRSS2-ERG fusion protein, human
• Transcriptional Regulator ERG

Topics

• Adult
• Aged
• Body Height
• Body Mass Index
• Body Weight
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Obesity (complications)
• Oncogene Proteins, Fusion (analysis, genetics, metabolism)
• Prospective Studies
• Prostatic Neoplasms (chemistry, epidemiology, etiology, genetics)
• Risk Factors
• Transcriptional Regulator ERG (analysis)